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Pim1 kinase regulates c-Kit gene translation.

Publication ,  Journal Article
An, N; Cen, B; Cai, H; Song, JH; Kraft, A; Kang, Y
Published in: Exp Hematol Oncol
2016

BACKGROUND: Receptor tyrosine kinase, c-Kit (CD117) plays a pivotal role in the maintenance and expansion of hematopoietic stem/progenitor cells (HSPCs). Additionally, over-expression and/or mutational activation of c-Kit have been implicated in numerous malignant diseases including acute myeloid leukemia. However, the translational regulation of c-Kit expression remains largely unknown. METHODS AND RESULTS: We demonstrated that loss of Pim1 led to specific down-regulation of c-Kit expression in HSPCs of Pim1-/- mice and Pim1-/-2-/-3-/- triple knockout (TKO) mice, and resulted in attenuated ERK and STAT3 signaling in response to stimulation with stem cell factor. Transduction of c-Kit restored the defects in colony forming capacity seen in HSPCs from Pim1-/- and TKO mice. Pharmacologic inhibition and genetic modification studies using human megakaryoblastic leukemia cells confirmed the regulation of c-Kit expression by Pim1 kinase: i.e., Pim1-specific shRNA knockdown down-regulated the expression of c-Kit whereas overexpression of Pim1 up-regulated the expression of c-Kit. Mechanistically, inhibition or knockout of Pim1 kinase did not affect the transcription of c-Kit gene. Pim1 kinase enhanced c-Kit 35S methionine labeling and increased the incorporation of c-Kit mRNAs into the polysomes and monosomes, demonstrating that Pim1 kinase regulates c-Kit expression at the translational level. CONCLUSIONS: Our study provides the first evidence that Pim1 regulates c-Kit gene translation and has important implications in hematopoietic stem cell transplantation and cancer treatment.

Duke Scholars

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Published In

Exp Hematol Oncol

DOI

ISSN

2162-3619

Publication Date

2016

Volume

5

Start / End Page

31

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3201 Cardiovascular medicine and haematology
 

Citation

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An, N., Cen, B., Cai, H., Song, J. H., Kraft, A., & Kang, Y. (2016). Pim1 kinase regulates c-Kit gene translation. Exp Hematol Oncol, 5, 31. https://doi.org/10.1186/s40164-016-0060-3
An, Ningfei, Bo Cen, Houjian Cai, Jin H. Song, Andrew Kraft, and Yubin Kang. “Pim1 kinase regulates c-Kit gene translation.Exp Hematol Oncol 5 (2016): 31. https://doi.org/10.1186/s40164-016-0060-3.
An N, Cen B, Cai H, Song JH, Kraft A, Kang Y. Pim1 kinase regulates c-Kit gene translation. Exp Hematol Oncol. 2016;5:31.
An, Ningfei, et al. “Pim1 kinase regulates c-Kit gene translation.Exp Hematol Oncol, vol. 5, 2016, p. 31. Pubmed, doi:10.1186/s40164-016-0060-3.
An N, Cen B, Cai H, Song JH, Kraft A, Kang Y. Pim1 kinase regulates c-Kit gene translation. Exp Hematol Oncol. 2016;5:31.
Journal cover image

Published In

Exp Hematol Oncol

DOI

ISSN

2162-3619

Publication Date

2016

Volume

5

Start / End Page

31

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3201 Cardiovascular medicine and haematology